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Fig. 2 | Molecular Neurodegeneration

Fig. 2

From: Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy

Fig. 2

Metformin treatment reduces tau phosphorylation in vivo. Total tau and phosphorylated tau (pTau) were analyzed in the cortex and hippocampus of 5 month old P301S mice treated with or without metformin for 4 months. a Western blot of phosphorylated and total tau in the cortex. Actin was analyzed as a loading control. b-g Quantitative analysis of pTau in the cortex (b, d, f, g) and hippocampus (c, e). Phosphorylated tau was analyzed using AT8 (b, c), anti-phospho-S262 tau (d, e), PHF-1 (f), AT270 (g) antibodies and normalized to total tau levels. Total tau was analyzed using Tau5 antibody. Bars represent the average ratio over total tau ± SEM. p < 0.05, Student t-test. Panel b: n = 11 / group. Panel c: Ctr, n = 10; Met, n = 11. Panel d: Ctr, n = 12; Met, n = 12. Panel e: Ctr, n = 7; Met, n = 6; Panel f-g: Ctr, n = 7; Met, n = 7. h-i Representative fluorescence images of AT8 immunoreactivity in the cortex of untreated and metformin-treated P301S mice. Scale bars: in H-I, 50 μm; in h’-i’, 150 μm. Panels h’ and i’ are magnification of squared areas in panels h and i. j. AT8 positive (AT8+) cells in the prefrontal cortex. k-l Representative fluorescence images of AT8 immunoreactivity in hippocampi of untreated and metformin-treated P301S mice. Scale bars: in k-l, 100 μm; in k’-l’, 200 μm. Panels k’ and l’ are magnification of squared areas in panels k and l, respectively. m-o AT8 positive (AT8+) cells in the hippocampus (m), granular zone (n) and dentate gyrus (o). Panel j: Ctr, n = 3; Met, n = 4; Panel m-o: Ctr, n = 3; Met, n = 5. In j and m-o, bars represent the average cell number / mm2 ± SEM. *p < 0.05, **p < 0.01, Student t-test

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